| 1. |
- Jacobs, Kevin B, et al.
(författare)
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Detectable clonal mosaicism and its relationship to aging and cancer.
- 2012
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Ingår i: Nature Genetics. - New York : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 44:6, s. 651-658
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Tidskriftsartikel (refereegranskat)abstract
- In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases.
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| 2. |
- Machiela, Mitchell J., et al.
(författare)
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Characterization of Large Structural Genetic Mosaicism in Human Autosomes
- 2015
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 96:3, s. 487-497
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Tidskriftsartikel (refereegranskat)abstract
- Analyses of genome-wide association study (GWAS) data have revealed that detectable genetic mosaicism involving large (>2 Mb) structural autosomal alterations occurs in a fraction of individuals. We present results for a set of 24,849 genotyped individuals (total GWAS set II [TGSII]) in whom 341 large autosomal abnormalities were observed in 168 (0.68%) individuals. Merging data from the new TGSII set with data from two prior reports (the Gene-Environment Association Studies and the total GWAS set I) generated a large dataset of 127,179 individuals; we then conducted a meta-analysis to investigate the patterns of detectable autosomal mosaicism (n = 1,315 events in 925 [0.73%] individuals). Restricting to events >2 Mb in size, we observed an increase in event frequency as event size decreased. The combined results underscore that the rate of detectable mosaicism increases with age (p value = 5.5 x 3 10(-31)) and is higher in men (p value = 0.002) but lower in participants of African ancestry (p value = 0.003). In a subset of 47 individuals from whom serial samples were collected up to 6 years apart, complex changes were noted over time and showed an overall increase in the proportion of mosaic cells as age increased. Our large combined sample allowed for a unique ability to characterize detectable genetic mosaicism involving large structural events and strengthens the emerging evidence of non-random erosion of the genome in the aging population.
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| 3. |
- Machiela, Mitchell J, et al.
(författare)
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Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome
- 2016
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events >2 Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases.
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| 4. |
- Bassinet, C., et al.
(författare)
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Retrospective radiation dosimetry using OSL of electronic components: Results of an inter-laboratory comparison
- 2014
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Ingår i: Radiation Measurements. - : Elsevier BV. - 1879-0925 .- 1350-4487. ; 71, s. 475-479
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Tidskriftsartikel (refereegranskat)abstract
- In the framework of the EU-FP7 MULTIBIODOSE project, two protocols using OSL of resistors removed from the circuit board of mobile phones were developed with the aim to use the resistors as fortuitous dosimeters in the event of a large scale radiological accident. This paper presents the results of an inter-laboratory comparison carried out under the umbrella of EURADOS. The two aims of this exercise were the validation of the MULTIBIODOSE protocols by a large number of laboratories and the dissemination of the method with the objective of preparing the basis for a network that could increase Europe's response capacity in the case of a mass casualty radiological emergency. Twelve institutes from eleven European countries and one institute from the USA, with various degrees of expertise in OSL dosimetry, took part in the OSL inter-laboratory comparison. Generally, a good agreement within uncertainties was observed between estimated and nominal doses. (C) 2014 Elsevier Ltd. All rights reserved.
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| 5. |
- Fattibene, P, et al.
(författare)
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The 4th international comparison on EPR dosimetry with tooth enamel Part 1: Report on the results
- 2011
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Ingår i: Radiation Measurements. - : Elsevier. - 1350-4487 .- 1879-0925. ; 46:9, s. 765-771
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents the results of the 4th International Comparison of in vitro electron paramagnetic resonance dosimetry with tooth enamel, where the performance parameters of tooth enamel dosimetry methods were compared among sixteen laboratories from all over the world. The participating laboratories were asked to determine a calibration curve with a set of tooth enamel powder samples provided by the organizers. Nine molar teeth extracted following medical indication from German donors and collected between 1997 and 2007 were prepared and irradiated at the Helmholtz Zentrum Munchen. Five out of six samples were irradiated at 0.1, 0.2, 0.5, 1.0 and 1.5 Gy air kerma; and one unirradiated sample was kept as control. The doses delivered to the individual samples were unknown to the participants, who were asked to measure each sample nine times, and to report the EPR signal response, the mass of aliquots measured, and the parameters of EPR signal acquisition and signal evaluation. Critical dose and detection limit were calculated by the organizers on the basis of the calibration-curve parameters obtained at every laboratory. For calibration curves obtained by measuring every calibration sample three times, the mean value of the detection limit was 205 mGy, ranging from 56 to 649 mGy. The participants were also invited to provide the signal response and the nominal dose of their current dose calibration curve (wherever available), the critical dose and detection limit of which were also calculated by the organizers.
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| 6. |
- Ainsbury, Elizabeth, et al.
(författare)
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Integration of new biological and physical retrospective dosimetry methods into EU emergency response plans - joint RENEB and EURADOS inter-laboratory comparisons
- 2017
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Ingår i: International Journal of Radiation Biology. - : Informa UK Limited. - 0955-3002 .- 1362-3095. ; 93:1, s. 99-109
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: RENEB, 'Realising the European Network of Biodosimetry and Physical Retrospective Dosimetry,' is a network for research and emergency response mutual assistance in biodosimetry within the EU. Within this extremely active network, a number of new dosimetry methods have recently been proposed or developed. There is a requirement to test and/or validate these candidate techniques and inter-comparison exercises are a well-established method for such validation. Materials and methods: The authors present details of inter-comparisons of four such new methods: dicentric chromosome analysis including telomere and centromere staining; the gene expression assay carried out in whole blood; Raman spectroscopy on blood lymphocytes, and detection of radiation induced thermoluminescent signals in glass screens taken from mobile phones. Results: In general the results show good agreement between the laboratories and methods within the expected levels of uncertainty, and thus demonstrate that there is a lot of potential for each of the candidate techniques. Conclusions: Further work is required before the new methods can be included within the suite of reliable dosimetry methods for use by RENEB partners and others in routine and emergency response scenarios.
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| 7. |
- Berndt, Sonja I, et al.
(författare)
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Large-scale fine mapping of the HNF1B locus and prostate cancer risk
- 2011
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 20:16, s. 3322-3329
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Tidskriftsartikel (refereegranskat)abstract
- Previous genome-wide association studies have identified two independent variants in HNF1B as susceptibility loci for prostate cancer risk. To fine-map common genetic variation in this region, we genotyped 79 single nucleotide polymorphisms (SNPs) in the 17q12 region harboring HNF1B in 10 272 prostate cancer cases and 9123 controls of European ancestry from 10 case-control studies as part of the Cancer Genetic Markers of Susceptibility (CGEMS) initiative. Ten SNPs were significantly related to prostate cancer risk at a genome-wide significance level of P < 5 × 10(-8) with the most significant association with rs4430796 (P = 1.62 × 10(-24)). However, risk within this first locus was not entirely explained by rs4430796. Although modestly correlated (r(2)= 0.64), rs7405696 was also associated with risk (P = 9.35 × 10(-23)) even after adjustment for rs4430769 (P = 0.007). As expected, rs11649743 was related to prostate cancer risk (P = 3.54 × 10(-8)); however, the association within this second locus was stronger for rs4794758 (P = 4.95 × 10(-10)), which explained all of the risk observed with rs11649743 when both SNPs were included in the same model (P = 0.32 for rs11649743; P = 0.002 for rs4794758). Sequential conditional analyses indicated that five SNPs (rs4430796, rs7405696, rs4794758, rs1016990 and rs3094509) together comprise the best model for risk in this region. This study demonstrates a complex relationship between variants in the HNF1B region and prostate cancer risk. Further studies are needed to investigate the biological basis of the association of variants in 17q12 with prostate cancer.
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| 8. |
- Yeager, Meredith, et al.
(författare)
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Identification of a new prostate cancer susceptibility locus on chromosome 8q24.
- 2009
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:10, s. 1055-7
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Tidskriftsartikel (refereegranskat)abstract
- We report a genome-wide association study in 10,286 cases and 9,135 controls of European ancestry in the Cancer Genetic Markers of Susceptibility (CGEMS) initiative. We identify a new association with prostate cancer risk on chromosome 8q24 (rs620861, P = 1.3 x 10(-10), heterozygote OR = 1.17, 95% CI 1.10-1.24; homozygote OR = 1.33, 95% CI 1.21-1.45). This defines a new locus associated with prostate cancer susceptibility on 8q24.
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| 10. |
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